We have developed two systems to stimulate nuclear DNA replication in the hepatocytes of unoperated rats. The first involves the infusion of a solution that contains thyroid hormones, the second, a dietary manipulation with amino acids. To learn about the stimulus that leads to DNA synthesis in normal liver, efforts will be made to determine how thyroid hormone and amino acids act in the two systems. We have found that the nuclei from regenerating liver after partial hepatectomy contain a DNA polymerase that is not present in normal liver nuclei. The goal of this project is to provide evidence for or against a replicative role for the regenerating nuclear enzyme.